rs73569592

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001363227.2(HGSNAT):c.1654A>C(p.Lys552Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00608 in 1,613,202 control chromosomes in the GnomAD database, including 550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 305 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 245 hom. )

Consequence

HGSNAT
NM_001363227.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 4.17

Publications

6 publications found

Variant links:

Genes affected

HGSNAT (HGNC:26527): (heparan-alpha-glucosaminide N-acetyltransferase) This gene encodes a lysosomal acetyltransferase, which is one of several enzymes involved in the lysosomal degradation of heparin sulfate. Mutations in this gene are associated with Sanfilippo syndrome C, one type of the lysosomal storage disease mucopolysaccaridosis III, which results from impaired degradation of heparan sulfate. [provided by RefSeq, Jan 2009]

HGSNAT Gene-Disease associations (from GenCC):

mucopolysaccharidosis type 3
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
mucopolysaccharidosis type 3C
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics, G2P
retinitis pigmentosa 73
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HGSNAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 8-43197696-A-C is Benign according to our data. Variant chr8-43197696-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 363150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363227.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HGSNAT	NM_152419.3	MANE Select	c.1567A>C	p.Lys523Gln	missense	Exon 16 of 18	NP_689632.2
HGSNAT	NM_001363227.2		c.1654A>C	p.Lys552Gln	missense	Exon 17 of 19	NP_001350156.1
HGSNAT	NM_001363228.2		c.1375A>C	p.Lys459Gln	missense	Exon 14 of 16	NP_001350157.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HGSNAT	ENST00000379644.9	TSL:2 MANE Select	c.1567A>C	p.Lys523Gln	missense	Exon 16 of 18	ENSP00000368965.4
HGSNAT	ENST00000519705.1	TSL:1	n.883A>C		non_coding_transcript_exon	Exon 2 of 4
HGSNAT	ENST00000902460.1		c.1768A>C	p.Lys590Gln	missense	Exon 17 of 19	ENSP00000572519.1

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5096

AN:

152090

Hom.:

304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.00856

AC:

2134

AN:

249284

AF XY:

0.00656

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.00461

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00446

GnomAD4 exome

AF:

0.00322

AC:

4706

AN:

1460994

Hom.:

245

Cov.:

AF XY:

0.00276

AC XY:

2006

AN XY:

726858

show subpopulations

African (AFR)

AF:

0.119

AC:

3960

AN:

33400

American (AMR)

AF:

0.00521

AC:

233

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000174

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000909

AC:

101

AN:

1111272

Other (OTH)

AF:

0.00641

AC:

387

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

218

435

653

870

1088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0335

AC:

5104

AN:

152208

Hom.:

305

Cov.:

AF XY:

0.0328

AC XY:

2441

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.118

AC:

4898

AN:

41498

American (AMR)

AF:

0.00981

AC:

150

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

67998

Other (OTH)

AF:

0.0170

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

234

468

701

935

1169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0130

Hom.:

250

Bravo

AF:

0.0372

ESP6500AA

AF:

0.114

AC:

418

ESP6500EA

AF:

0.000245

AC:

ExAC

AF:

0.0106

AC:

1284

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Mucopolysaccharidosis, MPS-III-C (2)

Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Benign

0.96

Eigen

Benign

0.13

Eigen_PC

Benign

0.036

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.88

PhyloP100

4.2

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.45

Sift

Benign

0.066

Sift4G

Benign

0.43

Vest4

0.42

MPC

0.15

ClinPred

0.035

GERP RS

4.3

gMVP

0.52

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.32

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over